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Blood, 15 July 2007, Vol. 110, No. 2, pp. 536-543. Prepublished online as a Blood First Edition Paper on March 15, 2007; DOI 10.1182/blood-2007-01-068395. This Article Full Text (PDF) All Versions of this Article: blood-2007-01-068395v1 110/2/536    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zauli, G. Articles by Secchiero, P. Search for Related Content PubMed PubMed Citation Articles by Zauli, G. Articles by Secchiero, P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 17, 2007 Accepted March 10, 2007 Osteoprotegerin increases leukocyte adhesion to endothelial cells both in vitro and in vivo Giorgio Zauli*, Federica Corallini, Fleur Bossi, Fabio Fischetti, Paolo Durigutto, Claudio Celeghini, Francesco Tedesco, and Paola Secchiero Department of Biomedicine, University of Trieste, Trieste, Italy Department of Physiology and Pathology, University of Trieste, Trieste, Italy Department of Morphology and Embryology, University of Ferrara, Ferrara, Italy * Corresponding author; email: zauli{at}units.it. Recombinant osteoprotegerin (OPG) promoted the adhesion of both primary polymorphonuclear neutrophils (PMN) and leukemic HL60 cells to endothelial cells. Leukocyte/endothelial cell adhesion was promoted by short (peak at 1 hour) pre-incubation of either endothelial cells or PMN with OPG, and the peak of pro-adhesive activity was observed in the same range of OPG concentrations detected in the sera of patients affected by cardiovascular diseases. While membrane RANKL and TRAIL, the cognate high-affinity ligands for OPG, were detected at significant levels on both PMN and HL60, they were not expressed on the surface of endothelial cells. However, pre-incubation of OPG with heparin abrogated its pro-adhesive activity, while pretreatment of endothelial cells with chondroitinase plus heparinases significantly decreased the pro-adhesive activity of OPG. Taken together, these findings suggest the involvement of both the ligand binding and the N-terminal heparin-binding domains of OPG in mediating its pro-adhesive activity. The relevance of these in vitro findings was underscored by in vivo experiments, in which the topical administration of recombinant OPG increased leukocyte rolling and adhesion to rat mesenteric post-capillary venules. Our data suggest that a pathological increase of OPG serum levels might play an important role in promoting leukocyte/endothelial cell adhesion. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Secchiero, F. Corallini, E. Rimondi, C. Chiaruttini, M. G. di Iasio, A. Rustighi, G. Del Sal, and G. Zauli Activation of the p53 pathway down-regulates the osteoprotegerin expression and release by vascular endothelial cells Blood, February 1, 2008; 111(3): 1287 - 1294. [Abstract] [Full Text] [PDF] D. J. Metcalf, T. D. Nightingale, H. L. Zenner, W. W. Lui-Roberts, and D. F. Cutler Formation and function of Weibel-Palade bodies J. Cell Sci., January 1, 2008; 121(1): 19 - 27. [Abstract] [Full Text] [PDF]

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